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Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

One hundred and twelve sites in 21 countries randomized participants. In total, 694 participants were randomized: four participants did not start treatment and 690 participants started treatment (346 in the TMC278 group and 344 in the efavirenz [control ] group).

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The analysis population included intent to treat (ITT) population defined as all randomized participants who received at least one dose of the study medication.

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 [ Time Frame: Week 48 ]

Measure Type

Primary

Measure Title

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48

Measure Description

Virological response is defined as confirmed plasma viral load less than (<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid [RNA]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load <50 copies/ml).

Time Frame

Week 48

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The ITT analysis set was considered the primary efficacy analysis set.

Reporting Groups

Description

TMC278

25 milligram (mg) tablet once daily for 96 weeks.

Efavirenz

600 mg once daily for 96 weeks.

Measured Values

TMC278

Efavirenz

Participants Analyzed [Units: Participants]

346

344

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 [Units: Participants]

Responder

287

285

Virologic failure

38

15

Discontinued due to Adverse Event (AE)

6

25

Discontinued due to other reason than AE

15

19

Statistical Analysis 1 for Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48

Groups [1]

All groups

Statistical Test Type [2]

Non-Inferiority or Equivalence

Statistical Method [3]

Regression, Logistic

P Value [4]

<0.0001

Difference in proportion of response [5]

-0.4

95% Confidence Interval

-5.9 to 5.2

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

Assuming a response rate of 75% at 48 weeks for both treatment groups, 340 subjects were needed per treatment (TMC278 or EFV) to establish non-inferiority of TMC278 versus EFV with a maximum allowable difference of 12% and a 1-sided significance level of 2.5%, to yield 95% power.

[2]

Details of power calculation, definition of non-inferiority margin, and other key parameters:

If the lower limit of the 95% 2-sided confidence interval of the difference in proportions (TMC278 – EFV) exceeds -12%, non-inferiority of TMC278 versus EFV can be concluded.

[3]

Other relevant method information, such as adjustments or degrees of freedom:

The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48

Measure Description

The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/ml (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/ml in the Wk48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/ml and subjects who had a switch in background regimen that was not permitted by the protocol.

Time Frame

Week 48

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The ITT analysis set was considered the primary efficacy analysis set.

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

No text entered.

[5]

Other relevant estimation information:

Difference in proportion responders was estimated through the logistic regression model.

3. Secondary:

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 [ Time Frame: Week 96 ]

Measure Type

Secondary

Measure Title

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96

Measure Description

No text entered.

Time Frame

Week 96

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The ITT analysis set was considered the primary efficacy analysis set.

Reporting Groups

Description

TMC278

25 milligram (mg) tablet once daily for 96 weeks.

Efavirenz

600 mg once daily for 96 weeks.

Measured Values

TMC278

Efavirenz

Participants Analyzed [Units: Participants]

346

344

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 [Units: Participants]

Responder

263

271

Virologic failure

45

16

Death

0

3

Discontinued due to AE

10

29

Discontinued due to other reason than AE

28

25

Statistical Analysis 1 for Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96

Groups [1]

All groups

Statistical Test Type [2]

Non-Inferiority or Equivalence

Statistical Method [3]

Regression, Logistic

P Value [4]

0.0055

Difference in proportion of response [5]

-3.2

95% Confidence Interval

-9.4 to 3.1

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

No text entered.

[2]

Details of power calculation, definition of non-inferiority margin, and other key parameters:

If the lower limit of the 95% 2-sided confidence interval of the difference in proportions (TMC278 – EFV) exceeds -12%, non-inferiority of TMC278 versus EFV can be concluded.

[3]

Other relevant method information, such as adjustments or degrees of freedom:

The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96

Measure Description

No text entered.

Time Frame

Week 96

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The Intent-to-Treat analysis set was considered the primary efficacy analysis set.

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

No text entered.

[5]

Other relevant estimation information:

No text entered.

5. Secondary:

Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96). [ Time Frame: Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit ]

Measure Type

Secondary

Measure Title

Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96).

Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Participants with at least 1 Post-Week 96 visit were included in the analysis.

No statistical analysis provided for Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96).

6. Secondary:

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48 [ Time Frame: Week 48 ]

Measure Type

Secondary

Measure Title

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48

Measure Description

No text entered.

Time Frame

Week 48

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The ITT analysis set was considered the primary efficacy analysis set.

Reporting Groups

Description

TMC278

25 milligram (mg) tablet once daily for 96 weeks.

Efavirenz

600 mg once daily for 96 weeks.

Measured Values

TMC278

Efavirenz

Participants Analyzed [Units: Participants]

346

344

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48 [Units: Participants]

297

293

No statistical analysis provided for Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48

7. Secondary:

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96 [ Time Frame: Week 96 ]

Measure Type

Secondary

Measure Title

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96

Measure Description

No text entered.

Time Frame

Week 96

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The ITT analysis set was considered the primary efficacy analysis set.

Reporting Groups

Description

TMC278

25 milligram (mg) tablet once daily for 96 weeks.

Efavirenz

600 mg once daily for 96 weeks.

Measured Values

TMC278

Efavirenz

Participants Analyzed [Units: Participants]

346

344

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96 [Units: Participants]

273

278

No statistical analysis provided for Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96

Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.

Time Frame

Baseline, Week 48, and Week 96

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The ITT analysis set was considered the primary efficacy analysis set.

Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure [ Time Frame: Week 96 ]

Measure Type

Secondary

Measure Title

Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The ITT analysis set was considered the primary efficacy analysis set. Here "N" (Number of Participants Analyzed) signifies number of Participants who were evaluable (had data) for this outcome measure.

Reporting Groups

Description

TMC278

25 milligram (mg) tablet once daily for 96 weeks.

Efavirenz

600 mg once daily for 96 weeks.

Measured Values

TMC278

Efavirenz

Participants Analyzed [Units: Participants]

52

18

Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure [Units: Participants]

Any RAM from Extended NNRTI RAMs list

29

9

NNRTI RAM: E138K

18

0

NNRTI RAM: K101E

5

0

NNRTI RAM: Y181C

5

0

NNRTI RAM: V90I

4

0

NNRTI RAM: V189I

4

0

NNRTI RAM: H221Y

4

0

NNRTI RAM: E138Q

3

0

NNRTI RAM: K103N

1

8

Any RAM from IAS-USA N(t)RTI RAMs list

31

5

N(t)RTI RAM: M184I

24

3

N(t)RTI RAM: M184V

7

3

N(t)RTI RAM: K065R

3

0

N(t)RTI RAM: K219E

3

0

N(t)RTI RAM: Y115F

2

0

No statistical analysis provided for Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure